TRANSLATIONAL THERAPEUTICS CORE PROJECT SUMMARY The Translational Therapeutics Core (TTC) will accelerate preclinical development of new therapeutics for Alzheimer?s disease (AD) and AD-related dementias (ADRD) through human target validation in the laboratories of stellar scientists identified through the rigorous selection process of the Harrington Discovery Institute (HDI) at University Hospitals. HDI is part of the Harrington Project for Discovery & Development, an international initiative designed to enable inventive scientists to advance their discoveries into novel medicines that will improve human health by providing funding and drug development support to help bridge the gap between basic discovery and the clinical realm. A critical aspect of this is human data towards target validation, through the realms of clinical experience, human genetics, and tissue expression. This is particularly logistically challenging in the field of AD/ADRD due to scarcity of quality tissue and disease complexity. The TTC will fill a critical void in the ability to develop new therapeutics for patients with AD/ADRD by providing this opportunity to researchers with promising preclinical programs, as well as funds with which to conduct the relevant analysis. Through this alliance with the other Cleveland Alzheimer?s Disease Research Center (CADRC) Cores the TTC will work with HDI to proactively provide this opportunity to scientists. The TTC will be led by Dr. Andrew Pieper, the Director of the Alzheimer?s Drug Discovery Foundation (ADDF) ? Harrington Scholar Program. The ADDF-Harrington Scholar Award supports scientists conducting research to develop drugs to prevent, treat, and cure AD/ADRD. The TTC team will work to identify currently or previously funded HDI scholars who are developing therapeutics for AD/ADRD for whom inclusion in this program would meaningfully accelerate development of a therapeutic intervention (Specific Aim 1) or who are focused on developing therapeutics for different diseases within a space that the TTC determines might be applicable to AD/ADRD (Specific Aim 2), and finally to broaden the scope of the program, identify scientists anywhere in the world who are not currently linked to HDI but are working on exceptionally promising work in the field of AD/ADRD whose therapeutic development program would be meaningfully accelerated by this opportunity (Specific Aim 3). By providing access and funds for target validation in human tissue using the growing biospecimen collections in the CADRC Biomarker and Neuropathology Cores, the TTC will enable the CADRC to meaningfully advance development of new treatments for patients. In addition, coordination with the CADRC Biomarker Core (BC) will enable the TTC to facilitate identification of markers related to new therapeutic approaches, which might be applied in future clinical trials or patient care. Finally, coordination with the Clinical Core (CC) of the CADRC will facilitate future early stage clinical trials, specifically pertaining to issues of target engagement and safety.